Background: Radiotherapy is widely used in contemporary head and neck cancer treatment protocols. The ability of head and neck radiotherapy (HNRT) to cause direct radiogenic destruction to the teeth is one of the most controversial topics in the field of oral oncology. Therefore, this systematic review aimed to investigate ionising radiation as an independent factor for physical and chemical changes on the dentine-enamel junction (DEJ), a pivotal dental topography for the onset and progression of radiation-related caries (RRC) and enamel delamination. Material and Methods: Systematic searches were conducted on three databases: Scopus, MEDLINE (Via PubMed) and Embase (Elsevier). Laboratory studies evaluating the effects of simulated or in vivo HNRT on the DEJ were included. The GRADE tool adapted for in vitro studies was used to assess the methodological quality. Results: Of the 154 initially selected studies, eight met the inclusion criteria, from which five studies were graded as high quality of evidence, two studies were graded as moderate quality and one as low quality. Two studies did